High surface-area materials with nanoscale dimensions are of special interest in applications where active site mediated chemical reactions play an important role, such as catalytic applications where a high contact area between reactants and catalyst is necessary in order to achieve high yield in a cost-effective manner. There is therefore a large interest in the preparation of nanoscale porous materials, showing increased specific areas with controlled textural (porosity and morphology) properties in the whole range of sizes, i.e. the microscale (below 2 nm) the mesoscale (2-50 nm) and the macroscales (above 50 nm). An example of a porous material is the well known materials such as the crystalline zeolites.
Within the field of porous materials improvements in surface area can speed adsorption rates in for example protein separation devices such as chromatography columns. Control of pore size can increase selectivity for certain products in catalytic reactions. Control of particle size or shape can improve the mechanical stability of a catalyst support as well. Through the discovery of synthesis mesoporous materials of ordered amorphous silica structures, it became possible to make structures with such improved properties. Mesoporous materials are generally referred to materials with silica or other metal oxide compositions displaying sharp pore size distributions in the mesoscale (1.5-50 nm).
The methods rely on self-assembling action of amphiphiles surfactant molecules, which under controlled conditions form ordered micellar systems, as described in U.S. Pat. No. 5,098,684. The surfactant micelles are hereon termed as the pore template or template. A surfactant is a molecule possessing a polar and non-polar group capable of forming micellar structures. Condensation of a suitable silica precursor around micellar species leads to a hybrid organic-silica composite stable through charge matching interactions. The material is rendered mesoporous typically through calcination although routes such as solvent extraction, which enable the recovery of the surfactant template, have also been utilized. It is not a pre-requisite in these preparation routes for the surfactant to be above its critical micellar concentration (CMC). However, in order to have an ordered structure micelles must form at some point during the synthesis process, typically during the hydrolysis and condensation of the silicate precursor.
Micelles may only form when the surfactant concentration is greater than the CMC and the temperature of the solution is above the so-called Krafft temperature. Thermodynamically, micelles form spontaneously as a result of the interplay between entropy and enthalpy. In water, the hydrophobic effect arising from the non-polar group is the driving force for micelle formation. Broadly speaking, above the CMC, the entropic penalty of assembling the surfactant molecules is less than the entropic penalty of “mixing” surfactant monomers with water molecules. Another driving force is enthalpic, such as the electrostatic interactions that occur between the polar parts of the surfactant (typically known as the headgroup).
Numerous studies have focused on the synthetic, structural, morphology and compositional control of ordered mesoporous materials.
The preparation of inorganic mesoporous materials as described in U.S. Pat. No. 5,102,643 includes the polymerization of inorganic monomers using a self-assembling amphiphiles surfactant as the template. AU2006231725 describe an alternate synthesis to mesoporous materials; however such methods utilize amphiphilic surfactants as template. Yu Min Sun et al., and references thereof, describes the preparation of mesoporous silica, but once again the use of a surfactant template is a requirement for the formation of ordered pores. KR20070024550 have described the synthesis of mesoporous silica with chiral morphologies using a chiral surfactant template. AU2006231725 describe an alternate synthesis to mesoporous materials; however such methods utilize amphiphilic surfactants as templates.
Only recently has the formation of mesoporous materials with chiral morphologies been reported. Che et al. [Nature, 2004] utilized chiral nematic N-lauroyl-amino acid surfactants and co-structure directing agents (CSDAs) for the synthesis of hexagonal mesophases with chiral morphologies. The role of the CSDA is to facilitate through charge matching the interaction between the organic micellar aggregates and the inorganic silica precursor. This preparation route has subsequently yielded near enantiopure morphologies, however chiral separation and related applications have not been efficiently achieved due to the pore geometry and the pore surface being absent of chirality.
There is a strong desire to provide porous materials capable of separating racemic mixtures, i.e. mixtures of optical isomers. For example, the drug bicalutamide, an oral non-steroidal anti-androgen used in the treatment of prostate cancer, shows enhanced activity towards androgen receptors when the drug is administered in its enantiopure form (R-bicalutamide). It is of commercial interest to develop efficient methods for the separation of such chiral molecules, or for their synthesis using chiral catalysts to their respective enantiopure compounds.
Mesoporous materials are much studied and used in a variety of other applications. In the biotechnology and pharmaceutical sectors the combination of high surface areas and controlled pore geometries can be utilized for delivery of active drug substances that would otherwise require complex, and often not effective and expensive excipients. Controlled drug release from porous structures may result in a reduction of the number of doses and frequency needed to achieve therapeutic results from a drug administration perspective and may solve problems of drug/dose compliance by patients of a prescribed drug regime. Additionally, mesoporous materials show potential applications within this industry to enhance the solubility of poorly soluble drugs.
The solubility of fat-soluble anticancer drugs is a major problem both from uptake and formulation perspectives.
In another application, the encapsulation of enzymes in the pores of mesoporous materials has led to the realization of “heterogeneous” enzyme catalysts, where catalyst recovery and purification are aided from the presence of a porous matrix.
In diagnostics, mesoporous materials have been successfully utilized fluorophores for immunofluorescence and immunohistochemistry, whereby the internal pore volume may be loaded with a fluorescent molecule such as for example molecules of the porphyrin family, fluorescein isothiocyanate and derivatives, or Alexa type fluorescent molecules. This may be attached to the internal walls of mesoporous materials electrostatically or covalently to prevent from leaching out from the porous structure. The external particle surface of a mesoporous material is capable through the introduction of adequate functional groups to support biological conjugates.
Furthermore multiple signals/conjugations may easily be detected through the use of fluorophore loaded particles possessing different stokes shifts. These materials offer sensitive multifunctional detection devices as a result of the high loading capacity of the mesoporous silica particles.
Mesoporous materials are also being investigated for applications in water desalination plants (albeit in combination with polymeric membranes) and as gas separation devices where the combination of functionalized surfaces and pore geometry offers selectivity towards a particular gas, for example in the purification of exhaust gases from NOx and other harmful waste products from catalytic reactions.
Mesoporous materials comprising folic acid may be used as a dietary supplement for the delivery of folic acid and other vitamin B derivatives. Folic acid has many uses in medicine like prevention of neural tube defects (NTDs). Folic acid and other B vitamins help break down homocysteine in the body. Homocysteine levels in the blood are strongly influenced by diet and genetic factors. Dietary folic acid and vitamins B-6 and B-12 have the greatest effects. Several studies have found that higher blood levels of B vitamins are related, at least in part, to lower concentrations of homocysteine. Other evidence shows that low blood levels of folic acid are linked with a higher risk of fatal coronary heart disease and stroke.
Folic acid and derivatives have been associated with a reduction in certain cancer types, such as; colorectal cancer, pancreatic cancer and postmenopausal breast cancer.
Folic acid uptake mechanisms are up regulated in many human cancers, including malignancies of the ovary, brain, kidney, breast, and lung. The folate receptor has a high affinity for folic acid which results in high uptake by up regulated cells, even at low folate loadings on the therapeutic agent. Because of these characteristics, folate conjugation has become a widely used strategy for targeting liposomes, plasmid complexes, nanoparticles, polymer micelles, and other polymer constructs for selective uptake by tumor cells. Folic acid must be internalized into cells via either receptor mediated endocytosis or carrier based uptake mechanisms.
Metal oxide mesoporous materials possessing compositions other than silica which can include nanoparticles of various kinds have a wide variety of potential uses in applications such as catalyst or catalyst supports, capturing gases, water purification, photocurrent switching, photo-cathode in dye-sensitized solar cells, molecular optoelectronic devices or genetic repair in combination.